“More than a decade after infection with the Gulu strain o


“More than a decade after infection with the Gulu strain of Sudan Ebola virus, persons in Uganda were found to have persistent immune responses. To the Editor: Ebola virus

is a highly virulent emerging pathogen and a causative agent of viral hemorrhagic fever.(1) Studies of the pathogenesis of Ebola virus infection in humans have indicated that recovery is largely dependent on the development of an immune response.(1)-(3) To investigate the persistence of immune response in humans, we examined levels of cytokine expression after in vitro whole-blood stimulation in persons 12 years after EPZ6438 infection with the Gulu strain of Sudan Ebola virus (SUDV-gul). The study was conducted in accordance with the Declaration of Helsinki and was approved by the Uganda Ministry of Health, the …”
“Rational models of cognition typically consider the abstract computational problems posed by the environment, assuming

that VX-770 people are capable of optimally solving those problems. This differs from more traditional formal models of cognition, which focus on the psychological processes responsible for behavior. A basic challenge for rational models is thus explaining how optimal solutions can be approximated by psychological processes. We outline a general strategy for answering this question, namely to explore the psychological plausibility of approximation algorithms developed in computer science and statistics. In particular, we argue that Monte Carlo methods provide a source of rational process PD184352 (CI-1040) models that connect optimal solutions to psychological processes. We support this argument through a detailed example. applying this approach to Anderson’s (1990, 1991) rational model of categorization (RMC), which involves a particularly challenging computational problem. Drawing on a connection between the RMC and ideas from nonparametric Bayesian statistics, we propose 2 alternative algorithms for approximate inference in this model. The algorithms we consider include Gibbs sampling. a procedure appropriate

when all stimuli are presented simultaneously, and particle filters, which sequentially approximate the posterior distribution with a small number of samples that are updated as new data become available. Applying these algorithms to several existing datasets shows that a particle filter with a single particle provides a good description of human inferences.”
“The Thrombolysis in Myocardial Infarction (TIMI) study group, an academic research organization, was formed in 1984 with initial support from the National Heart, Lung, and Blood Institute. Its initial goal was to compare the effects of the then-new thrombolytic agent, recombinant tissue plasminogen activator, with streptokinase. The TIMI study group has remained active since then and has completed 50 multicenter clinical trials.

These results provide a comprehensive antigenic profile for H5N1

These results provide a comprehensive antigenic profile for H5N1 virus strains circulating in recent years and will facilitate the recognition of emerging antigenic variants of H5N1 virus and aid in the selection of vaccine strains.”
“The CACNA1F gene encodes the pore-forming

subunit of the L-type Ca(v)1.4 voltage-gated calcium channel (VGCC) and plays a central role in tonic vesicular release at photoreceptor ribbon synapses. The main objective of this study was to examine the effects of temperature on human Ca(v)1.4 cDNA clone VGCCs. With 20 mM Ba2+ as charge carrier, increasing the temperature from 23 degrees C to 37 degrees Fulvestrant order C increases whole-cell conductance, shifts the voltage-dependence Entinostat solubility dmso of activation to more hyperpolarized voltages, and accelerates the degree of recovery from inactivation over a given time, but does not significantly alter the half-inactivation potential (V-h). The window current for Ca(v)1.4 was also shifted to more hyperpolarized voltages, observable from similar to-35 mV to +20 mV at 37 degrees C in 20 mM Ba2+. Several comparable results were observed when characterizing Ca(v)1.2 at temperatures ranging from 23 degrees C to 37 degrees C. However, one difference between Ca(v)1.4 and Ca(v)1.2 was the temperature dependence of voltage-dependent inactivation kinetics. Increasing temperature from 23 degrees C to 37 degrees C accelerates

Ca(v)1.4 inactivation kinetics approximate to 50-fold, whereas Ca(v)1.2 only accelerates approximate to 10-fold over the same temperature range. The time constant of inactivation (tau(h)) temperature coefficient (Q(10)) was 18.8 for Ca(v)1.4 over a temperature range of 23 degrees to 33 degrees C (corresponding to an activation energy E-a=221 kJ/mol), compared with Ca(v)1.2 with a Q(10) of 3 (E-a=90 kJ/mol) recorded under identical conditions. C-X-C chemokine receptor type 7 (CXCR-7) In addition, Ca(v)1.4 was also tested using 2 mM Ca2+ as a charge carrier and similar changes in current-voltage Boltzmann

parameters and gating kinetics were observed. Hence, despite the accelerated inactivation kinetics of Ca(v)1.4 channels observed at near physiological temperatures the window current is preserved and could allow for tonic glutamate release from photoreceptors in the retina during dark adapted conditions. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Human endogenous retroviruses (HERVs) account for up to 9% of the human genome and include more than 800 elements related to betaretroviruses. While mouse mammary tumor virus (MMTV) is the accepted etiological agent of mammary tumors in mice, the role of retroviral elements in human breast cancer remains elusive. Here, we performed a comprehensive microarray-based analysis of overall retroviral transcriptional activities in 46 mammary gland tissue specimens representing pairs of nonmalignant and tumor samples from 23 patients.

Cannabidiol significantly prevented infarction and MPO activity a

Cannabidiol significantly prevented infarction and MPO activity at 20 h after reperfusion. These effects of cannabidiol were not inhibited by either SR141716 or AM630. Cannabidiol inhibited the MPO-positive cells expressing HMGB1 and also decreased the expression level of HMGB1 in plasma. In addition, cannabidiol decreased

the number of lba1- and GFAP-positive cells at 3 days after cerebral ischemia. Moreover, cannabidiol improved neurological score CH5183284 and motor coordination on the rota-rod test. Our results suggest that cannabidiol inhibits monocyte/macropharge expressing HMGB1 followed by preventing glial activation and neurological impairment induced by cerebral ischemia. Cannabidiol will open new therapeutic possibilities for post-ischemic injury via HMGB1-inhibiting mechanism. (C) 2008 Published by Elsevier Ltd.”
“Objective: Cardiac surgery with cardiopulmonary bypass for correction of congenital heart disease in neonates and small infants is associated with considerable neurologic sequelae. We Ro 61-8048 nmr assessed the extent to which mixed venous oxygen saturation as a measure for adequacy of perfusion, reflects the oxygenation status of upper and lower body compartments. Moreover, we evaluated potential

benefits of near-infrared spectroscopic monitoring of regional tissue oxygenation.

Methods: Twenty patients (body weight, 10 kg) undergoing open cardiac procedures with cardiopulmonary bypass were enrolled. Blood samples were obtained in parallel from inferior and superior caval vein cannulas and mixed venous line and assessed for venous oxygen saturation Phosphoribosylglycinamide formyltransferase and lactate levels. Data were compared to simultaneously measured tissue oxygenation indices obtained by near-infrared spectroscopy

from brain and lower limb.

Results: Venous oxygen saturation was lower and lactate concentration higher in blood from superior relative to inferior venous line. Mixed venous oxygen saturation correlated with venous oxygen saturation from inferior venous line and tissue oxygenation index of lower limb. No correlation was found between mixed venous oxygen saturation and venous oxygen saturation from superior venous line or cerebral tissue oxygenation index.

Conclusion: In neonates and small infants undergoing cardiac surgery with cardiopulmonary bypass, considerable regional differences exist in venous oxygen saturation. Mixed venous oxygen saturation primarily represents lower-torso oxygen status but poorly reflects and systematically overestimates upper-body oxygenation. Near-infrared spectroscopy yields additional information on regional oxygenation and may be valuable in early and sensitive detection of regional malperfusion in critical organs such as the brain.

The amount of long-term potentiation was decreased by 49% in trea

The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Ezrin

cross-links plasma membrane proteins with the actin cytoskeleton. In the kidney, ezrin mainly localizes at the brush border membrane of proximal tubules with the scaffolding protein, Na+/H+ exchanger regulatory factor (NHERF) 1. NHERF1 interacts Evofosfamide cost with the sodium/phosphate cotransporter, Npt2a. Defects in NHERF1 or Npt2a in mice cause hypophosphatemia. Here we studied the physiological role of ezrin in renal phosphate reabsorption using ezrin knockdown mice (Vil2). Ruxolitinib in vivo These mice exhibit hypophosphatemia, hypocalcemia, and osteomalacia. The reduced plasma phosphate concentrations were ascribed to defects

in urinary phosphate reabsorption. Immunofluorescence and immunoblotting indicated a marked reduction in renal Npt2a and NHERF1 expression at the apical membrane of proximal tubules in the knockdown mice. On the other hand, urinary loss of calcium SB-3CT was not found in Vil2 mice. Plasma concentrations of 1,25-dihydroxyvitamin D were elevated following reduced plasma phosphate levels, and mRNA of the vitamin D-dependent TRPV6

calcium channel were significantly increased in the duodenum of knockdown mice. Expression of TRPV6 at the apical membrane, however, was significantly decreased. Furthermore, tibial bone mineral density was significantly lower in both the adult and young Vil2 mice. These results suggest that ezrin is required for the regulation of systemic phosphate and calcium homeostasis in vivo. Kidney International (2012) 83, 41-49; doi:10.1038/ki.2012.308; published online 15 August 2012″
“Humor and laughter can positively influence mood, promote optimism and lead to a change of perspective. Six patients with major depression participated in a group training program specifically designed to enhance humor abilities. After 8 weeks of training, short-term mood improvement was observed and the patients considered themselves more capable of using humor as a coping strategy. Acquired humor skills also helped to sustain the patients’ motivation throughout the training period. In light of these encouraging findings, further studies to compare the effectiveness of the humor training with the effectiveness of other types of intervention and to assess its potential long-term effects seem warranted. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

In subsequent procedures, 31 patients without hypoplastic left he

In subsequent procedures, 31 patients without hypoplastic left heart syndrome KPT-330 order underwent superior cavopulmonary anastomosis and 5 biventricular repair. Overall transplant-free survival was not different between groups (P = .119) but trended to be higher in patients with a systemic or substantial left ventricle remnant contributing to cardiac output (P = .082).

Conclusions: Early and long-term survivals

and postoperative complications were similar between patients with and without hypoplastic left heart syndrome undergoing a Norwood operation. Recurrent aortic arch obstruction was common in both groups but more prevalent in patients without hypoplastic left heart syndrome. (J Thorac Cardiovasc Surg 2012;144:166-72)”
“Objective: Interstage mortality

has been reported in 10% to 25% of hospital survivors after single-ventricle palliation. The purpose of this study was to examine the impact of feeding modality at discharge after single-ventricle palliation on interstage mortality.

Methods: We conducted a retrospective review of all neonates undergoing single-ventricle palliation from January 2003 to January 2010. A total of 334 patients (90%) survived to hospital discharge, QNZ order comprising the study group. Preoperative, operative, and postoperative variables were examined, including feeding method at discharge. Multivariate Poisson regression models were constructed to estimate the relative risk of interstage mortality.

Results: Of 334 patients, 56 (17%) underwent gastrostomy tube +/- Nissen. There was a statistically significant increase in interstage mortality for patients who underwent gastrostomy tube +/- Nissen compared with patients who did not (relative risk, 2.38; 95% confidence interval, 1.05-5.40; P = .04]). Of the 278 patients who were not fed via a gastrostomy tube +/- Nissen, 190 (68%) were fed with nasogastric feedings and 88 (32%) were fed entirely by mouth. There was no difference enough in interstage mortality

between these 2 groups (relative risk, 0.92; 95% confidence interval, 0.31-2.73; P = .89).

Conclusions: Neonates undergoing single-ventricle palliation who require gastrostomy tube +/- Nissen are at an increased risk of interstage mortality. The need for gastrostomy tube +/- Nissen in this population may be a marker for other unmeasured comorbidities that place them at an increased risk of interstage mortality. Discharge with nasogastric feeds does not increase the risk of interstage mortality. (J Thorac Cardiovasc Surg 2012;144:173-7)”
“Objective: Cardiopulmonary bypass is associated with ischemia-reperfusion injury to multiple organs. We aimed to evaluate whether remote ischemic preconditioning performed the day before surgery for congenital heart disease with cardiopulmonary bypass attenuates the postoperative inflammatory response and myocardial dysfunction.

Methods: This was a prospective, randomized, single-blind, controlled trial.

CONCLUSION:

CONCLUSION: Linsitinib ic50 AMMs, as defined by 2000 WHO, are biologically heterogeneous. Recurrence-free survival can be further stratified by location and histological parameters,

especially mitotic count, brain invasion, and Ki67 labeling index. Not only brain invasion, but also the presence or absence of brain tissue in surgical specimens should be reported, because the absence of brain invasion, when brain tissue is identified, provides very important positive prognostic information.”
“Neutral ceramidase (NCDase) and sphingosine kinases (SphKs) are key enzymes regulating cellular sphingosine-1-phosphate (S1P) levels. In this study we found that stress factor-induced apoptosis of rat renal mesangial cells was significantly reduced by dexamethasone treatment. Concomitantly, dexamethasone increased cellular S1P levels, suggesting an activation of sphingolipid-metabolizing enzymes. The cell-protective effect of glucocorticoids was reversed by a SphK inhibitor, was completely absent in SphK1-deficient cells, and was associated with upregulated mRNA and protein expression of NCDase and SphK1. Additionally, in vivo experiments in mice showed that dexamethasone also upregulated SphK1 mRNA and activity, and NCDase protein expression in the kidney. Fragments (2285, 1724,

and 1126 bp) of the rat NCDase promoter linked to a luciferase reporter were transfected into rat kidney fibroblasts and mesangial cells. There was enhanced NCDase promoter activity upon glucocorticoids treatment that was abolished by the glucocorticoid receptor antagonist RU-486. Single and double mutations Osimertinib price of the two putative glucocorticoid response element sites within the promoter reduced the dexamethasone effect, suggesting that both glucocorticoid response elements are functionally active and required for induction. Our study shows that glucocorticoids exert a protective effect on stress-induced mesangial cell from apoptosis in vitro and in vivo by upregulating NCDase and SphK1 expression and activity, resulting in enhanced levels of the protective

lipid second messenger S1P. Kidney International (2010) 77, 870-879; doi:10.1038/ki.2010.62; published online 10 March 2010″
“BACKGROUND: Sciatica is typically a clear-cut symptom complex commonly related to an impingement at the spinal nerve level. Etiologies of sciatic neuropathy outside the neural foramina are uncommon.

OBJECTIVE: To describe 4 patients presenting with radiating leg pain due to sciatic nerve involvement, all with a vascular etiology.

METHODS: Four patients presenting with neuropathic pain were retrospectively reviewed. Preoperative 3 Tesla magnetic resonance imaging was used to identify these lesions, which most commonly showed diffuse T2 changes with nerve enhancement upon administration of contrast.

RESULTS: Exploration revealed vascular lesions. All patients went on to external and limited internal neurolysis of the involved sciatic nerve segment.

Extraarticular manifestations and radiological

scores wer

Extraarticular manifestations and radiological

scores were also recorded. The mean (SD) age was 51.7 +/- A 6.5 years in group I and 52.1 +/- A 6.1 years in group II patients (p > 0.05). The median disease durations were higher in group II than group I [8.0 (2-30) vs. 13 (3-35) years, respectively, p = 0.04]. Presence of RF [13(61.9 %) vs. 20(100 %) p = 0.001] and extraarticular involvement [5(25 %) vs. 13(65 %) p = 0.01] were higher in group II patients. When Ig-RF subgroups analyzed, all subgroup (IgA, IgM, IgG) levels were higher in group II (p = 0.001, p = 0.05, p = 0.001). IgA-RF levels were significantly high in patients with extraarticular involvement (p = 0.04). Association between high RF levels and having extraarticular manifestations in RA patients may largely be attributed to the IgA isotype.”
“Vitamin learn more D is a steroid hormone see more with pleiotropic effects. The association between serum 25-hydroxyvitamin D level [25(OH) D] and lupus nephritis are not clearly known. We aim to determine serum 25(OH) D levels in patients with inactive SLE, active SLE without lupus nephritis (LN) and active SLE with LN and to identify clinical predictor of vitamin D deficiency. One hundred and eight SLE patients were included. Patients were classified as Group (Gr) 1, 2 and 3 if

they had SLE disease activity index (SLEDAI) < 3, a parts per thousand yen3 but no LN and a parts per thousand yen3 with LN. Important baseline

characteristics were collected. 25(OH) D was measured by high performance liquid chromatography (HPLC). SLEDAI in Gr1, Gr2 and Gr3 was 0.7 (0.9), 5.6 (2.3) and 9.2 (5.2), respectively. 43.5 % had vitamin D insufficiency and 29.6 % had vitamin D deficiency. Mean 25(OH) D in each groups was 28.3 (8.0), 26.7 (9.5) and 19.9 (7.6) ng/ml (p < 0.001 comparing Gr1 and 3) (p = 0.003 comparing Gr2 and 3). Vitamin D deficiency was found in 11.1, 22.2 and 55.6 % of Gr1, 2 and 3. Linear regression analysis found that 25(OH) D was significantly BCKDHA correlated with serum albumin (r = 0.28, p = 0.004), inversely correlated with SLEDAI (r = -0.22, p = 0.03) and urinary protein creatinine index (UPCI) (r = -0.28, p = 0.005), but not with sun exposure score, body mass index and estimated GFR. Only UPCI was significantly inversely correlated with 25(OH) D (p = 0.02) from multiple linear regression. LN was a significant predictor of vitamin D deficiency from multivariate logistic regression (OR 5.97; p = 0.006). Vitamin D deficiency and insufficiency was found in 93 and 86 % of LN with proteinuria a parts per thousand yen and < 500 mg/day. We conclude that SLE patients with LN have significantly lower vitamin D level than inactive SLE and active SLE without LN. Hence, nephritis is a significant predictor of vitamin D deficiency in SLE patients.

(C) 2008 Elsevier Inc All rights reserved “
“Multiple syste

(C) 2008 Elsevier Inc. All rights reserved.”
“Multiple system atrophy is a sporadic, progressive, neurodegenerative disease characterized by an oligodendroglial accumulation of alpha-synuclein (alpha-syn). The mechanisms underlying the oligodendroglial accumulation of alpha-syn in the brains of patients with multiple system atrophy have attracted a great ACP-196 clinical trial deal of interest, given the primarily neuronal role reported for this protein. We examined the interactions between neuronal and oligodendroglial

alpha-syn in the progeny of crosses between parental transgenic (tg) mouse lines that express alpha-syn either under the oligodendroglial-specific myelin-basic protein promoter (MBP1-h alpha-syn tg) or under the neuronal platelet-derived growth factor promoter (PDGF-h alpha-syn tg). Our results demonstrate www.selleckchem.com/products/dabrafenib-gsk2118436.html that progeny from the cross [h alpha-syn double (dbl) tg mice] displayed a robust redistribution of alpha-syn accumulation, with a relocalization from a neuronal or a mixed neuronal/oligodendroglial alpha-syn expression to a more oligodendroglial pattern in both the neocortex and the basal ganglia that closely resembled the parental MBP-h alpha-syn tg line. The h alpha-syn

dbl tg mice also displayed motor deficits, concomitant with reduced levels of tyrosine hydroxylase and augmented neuropathological alterations in the basal ganglia. These results suggest that the central nervous system milieu in the h alpha-syn dbl tg mice favors an oligodendroglial accumulation of alpha-syn. This model represents an important tool to examine the interactions between neuronal

and oligodendrocytic Sucrase alpha-syn in diseases such as multiple system atrophy. NeuroReport 23:259-264 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“A substantial body of evidence has accumulated linking an increased incidence of cardiovascular disease in patients with acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). A multitude of novel risk factors related to decreased kidney function might interact with the renal and systemic immune systems involved in renal injury and repair to participate in accelerated atherogenesis (Immune inflammation-Renal injuryAtherosclerosis-the IRA Paradigm). In this review, we will discuss several of these novel risk factors and present the potential for the role of the immune-inflammatory system in accelerated atherosclerosis of kidney disease. Kidney International (2011) 80, 453-463; doi:10.1038/ki.2011.178; published online 22 June 2011″
“Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing.

At 28 days, the primary outcome was death among patients who did

At 28 days, the primary outcome was death among patients who did not have check details a response to a corticotropin test.

Results: Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone

group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group

(31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.

Conclusions: Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened BLZ945 manufacturer reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.).”
“Recently, there has been a rapid gain of interest in the availability, applicability, and integration of different types of spatial data for environment and health issues. The INSPIRE Directive (Directive 2007/2/EC) aims at providing better and easily accessible spatial information in Europe for the formulation and implementation

of community policy on the environment by triggering the creation of a European spatial information infrastructure that delivers integrated spatial information services to potential users. Human biomonitoring (HBM) significantly contributes to the already existing data on environment and health because of its specific nature of providing information on the internal dose of chemicals rather than their mere presence in different environmental compartments. SSR128129E However, due to the intrinsic nature of HBM data, a number of issues need to be dealt with if HBM data are to be used to its full capacity in a geographic information systems (GIS) environment and within the INSPIRE directive. The current article highlights some of these issues, and discusses a number of options to improve the geographical relevance of HBM data for their optimal use within the INSPIRE Directive framework. The main aim of this publication is to illustrate that HBM has a significant contribution to make to the INSPIRE Directive, although some kind of data aggregation will be necessary to protect individual privacy.

CONCLUSIONS

Injectable diacetylmorphine was more effec

CONCLUSIONS

Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)”
“Viral infections often produce double-stranded RNA (dsRNA), which in turn triggers potent antiviral responses, including the global repression of protein synthesis mediated by protein kinase R (PKR) click here and 2′-5′ oligoadenylate synthetase (OAS). As a consequence, many viruses have evolved genes, such as those encoding dsRNA-binding proteins, which counteract these pathways. Human cytomegalovirus

(HCMV) encodes two related proteins, pTRS1 and pIRS1, which bind dsRNA and can prevent activation of the PKR and OAS pathways. HCMV mutants lacking either IRS1 or TRS1 replicate at least moderately well in cell culture. However, as we demonstrate in the present study, an HCMV mutant lacking both IRS1 and TRS1 (HCMV[Delta I/Delta T]) has a severe replication defect. Infection with HCMV[Delta I/Delta T] results in a profound inhibition of overall and viral protein synthesis, as well as increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2 alpha). The vaccinia virus E3L gene can substitute for IRS1 or TRS1, enabling HCMV replication.

Despite the accumulation of dsRNA in HCMV-infected cells, the OAS pathway remains inactive, even in HCMV[Delta I/Delta T]-infected cells. These results suggest that PKR-mediated phosphorylation CFTRinh-172 of eIF2 alpha is the dominant Isotretinoin dsRNA-activated pathway responsible for inhibition of protein synthesis and HCMV replication in the absence of both IRS1 and TRS1 and that the requirement for evasion of the PKR pathway likely explains the necessity for IRS1 or TRS1 for productive infection.”
“A

62-year-old woman with osteoarthritis presents with a 7-month history of progressively worsening left hip pain radiating to the groin, 8 months after undergoing total left-hip arthroplasty. The pain has not responded to nonsteroidal antiinflammatory drugs. Physical examination reveals a sinus tract overlying her left hip. Her leukocyte count is 8000 per cubic millimeter, and the C-reactive protein (CRP) level is 15.5 mg per liter. A radiograph shows loosening of the prosthesis at the bone-cement interface. Synovial-fluid aspirate shows 15×10(3) cells per cubic millimeter (89% neutrophils); cultures of an aspirate from the hip grow Staphylococcus epidermidis. How should her case be managed?”
“The mature arenavirus envelope glycoprotein GPC is a tripartite complex comprising a stable signal peptide (SSP) in addition to the receptor-binding (G1) and transmembrane fusion (G2) subunits. We have shown previously that SSP is a key element in GPC-mediated membrane fusion, and that GPC sensitivity to acidic pH is modulated in part through the lysine residue at position 33 in the ectodomain loop of SSP (J. York and J. H. Nunberg, J. Virol.